Newborn Screening for Isovaleric Acidemia: Treatment With Pivalate-Generating Antibiotics Contributed to False C5-Carnitine Positivity in a Chinese Population

Abstract

Background: Newborn screening (NBS) for isovaleric acidemia (IVA) is implemented via tandem mass spectrometry (MS/MS), but false-positive results are still common. In addition, NBS for IVA is limited by a lack of suitable biomarkers, especially after the use of pivaloylester-containing antibiotics.

Methods: We conducted a retrospective cohort study to explore the clinical correlation between antibiotic administration and false-positive results for isovalerylcarnitine (C5).

Results: A total of 509,313 newborns were recruited from the initial NBS study, only one of whom underwent genetic confirmation, conducted between 2015 and 2020. Significant associations between false-positive C5-carnitine screening results and treatment with pivalate-generating antibiotics were identified with retrospective analysis.

Conclusions: The current results highlight the detrimental effects of false-positive C5-carnitine screening results. Unless the licensing of pivalate-generating antibiotics for use during the neonatal period is reconsidered, a second-tier test for C5 determination will be necessary.

Keywords: isovaleric acidemia; pivalate‐generating antibiotics; second‐tier screening.